A prototype negative pi meson generator, the Stanford Medical Pion Generator (SMPG), for potential application in the treatment of human cancer has been constructed at Stanford under NSF RANN GI-35007. This device will be available for pion production approximately 1 January 1974 by coupling with the existing Stanford Mark III linear electron accelerator which may be operated at 500 MeV and 5 microamperes (Phase I). This combination will produce a pion output of approximately 9 rads per minute within a pion stopping region 1 cm in diameter and 1 cm in length. In about May of 1975, the SMPG described herein will be coupled with the Stanford superconducting linear accelerator which will produce a 500 MeV electron beam at 500 microamperes. With this combination, the SMPG will produce a pion output of 1,200 rads per minute within a stopping region 2.5 cm in length and 1 cm in diameter, or 20-30 rads per minute in a stopping volume of 1,000 cc (Phase II). With this proposal we will commence the detailed dosimetry of pions during Phase I and start the investigation of biological effects in tissue culture and some animal experiments in order to develop the characterization of the physical and biological properties of the pion beam, particularly with reference to the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and repair within specified regions of the beam. During Phase II, these experiments will be extended and, in addition, a comprehensive study will be undertaken of the fine structure of RBE and its relationship with dose in normal and neoplastic tissues. In these studies, the criterion of radiation damage for several relevant normal tissues will be tissue tolerance and for tumors, cell survival. Since a unique radial geometry employing 60 converging pion pencil beams will be used to develop the pion stopping region, preliminary treatment planning and the methodology for confirming the position of the pion stopping region within a patient will also be investigated.